tbuckley/cabot-search huggingface dataset:
Abstract 12217: Effect of Repeated Binge Drinking in Mid-Life Adults on Vascular Function
Authors: Carolina M Pusec, Brooks A Hibner, Yuliya Drab, Mariann R Piano, Shane A Phillips, Chueh-Lung Hwang
Journal: Circulation (2022)

Introduction: Age-related changes in vascular function, including endothelial dysfunction and arterial stiffening, contribute to the development of cardiovascular disease. “Mid-life adults”, defined as age 50-64, begin to show signs of vascular aging. One in five mid-life adults engage in binge drinking and our previous studies in young adults showed that repeated binge drinking was associated with endothelial dysfunction and arterial stiffening. However, it is unclear how binge drinking influences vascular function in aged individuals. Therefore, the purpose of this study is to investigate endothelial function and arterial stiffness in mid-life adults who binge drink regularly (binge drinkers) compared to those who did not drink alcohol (alcohol abstainers). Methods: Twelve apparently healthy mid-life men and postmenopausal women, with no smoking history were included in this study (mean±SEM, age: 57±1 years, body mass index: 26.0±0.8 kg/cm 2 , systolic blood pressure: 119±5 mmHg). Alcohol use was assessed by the Alcohol Use Disorders Identification Test (AUDIT) and dried blood spot phosphatidylethanol. Endothelial function was assessed by brachial artery response to reactive hyperemia (flow-mediated dilation, FMD) via ultrasonography. Arterial stiffness was assessed by carotid to femoral pulse wave velocity (cfPWV) via use of the cuff-based SphygmoCor Xcel. Results: Binge drinkers (n=6) had an AUDIT score≥5 (11.8±2.1) and positive phosphatidylethanol level (162±103 ng/mL), while alcohol abstainers (n=6) had an AUDIT score≤1 (0.8±0.2) and negative phosphatidylethanol level. Compared to alcohol abstainers, binge drinkers had a lower brachial artery FMD (alcohol abstainers vs. binge drinkers: 9.8±1.2% vs. 5.1±0.9%, P=0.01), but similar cfPWV (7.2±0.7 vs. 7.0±0.5 m/sec, P=0.8). Conclusions: Our results indicate that compared to mid-life adult alcohol abstainers, binge drinkers had lower endothelial function, but similar arterial stiffness. These findings suggest that repeated binge drinking may further impair endothelial function throughout the aging process.
Abstract 12441: Association Between Habitual Consumption of Meal Replacement Products And Cardiac Mortality Risk in US Adults: A Prospective Study
Authors: Yuxuan Zhao, Haiming Yang, Xiao Meng, Yueqing Wang, Mingyu Song, Dianjianyi Sun
Journal: Circulation (2022)

Introduction : Little is known about the long-term association between Habitual Consumption of Meal Replacement Products and the risk of cardiac mortality. Methods: Analyses were performed using data from NHANES 2003 to 2006 and linked mortality data, consisting of 5292 participants aged 20 to 84 years old. The frequency of MR consumption was categorized into 3 groups according to the food frequency questionnaire: seldom, often and almost every day. Linked cardiac mortality records from the National Death Index were documented till Dec 31, 2019. Cox regression models were fitted controlled for demographic characteristics, social-economic factors, disease histories, and lifestyle factors. Results: At baseline, the overall percentage of American adults consuming MR products often and almost every day were 10.39% and 3.34%. During a median follow-up of 10.75 years, 98 death events due to heart diseases were recorded. Compared to respondents who seldom consumed MR products, respondents consuming MR products almost every day were associated with higher cardiac mortality risk (Adjusted HR and 95% confidence intervals: 2.51, 1.07 to 5.91, P value=0.035). Conclusion: Habitual consumption of MR products might be associated with higher cardiac mortality risk.
Abstract 121: Covid-19 Cardiac Arrest: Resuscitate Or Not?
Authors: Claudia M Ramirez, Mohamed Ziad, Angelica Almaguer, Sushen Bhalla, Jesus Gonzalez, Ailine Canete Cruz, Ndiya Emeaba, David Akinwale, Daryelle Varon, Abbas Alshami, Joseph Varon
Journal: Circulation (2022)

Introduction: Coronavirus disease 2019 (COVID-19) has been associated with high in-hospital mortality. Since the implementation of guidelines and improvement in the quality of cardiopulmonary resuscitation (CPR), the survival rate for non-COVID-19 patients has improved. There is, however, scarce data regarding in-hospital cardiac arrest outcomes in COVID-19 patients. This study aimed to investigate cardiac arrest outcomes in patients hospitalized for COVID-19. Methods: Retrospective study of the data of 994 adult patients admitted to a single-center high acuity critical care COVID -19 unit between March 2020 and February 2022 with COVID-19 diagnosis. Patients who underwent CPR were identified. Resuscitation registers and demographic information were obtained. The primary outcome was survival to hospital discharge. Secondary assessments were the initial rhythm and duration of CPR. Descriptive statistics were utilized. Results: A total of 994 COVID-19 patients were included in the study. 129 (13%) had a cardiac arrest and underwent CPR. Two patients survived hospital discharge (1.6%). Of them, 91(70.5%) were male. Mean age was 68.6 (+/- 13.5) years. Median BMI was 29.1 [25.8-35.7] Kg/m 2 . The most frequent comorbidity was hypertension in 59 patients (46.1%), followed by diabetes type 2 in 30 patients (23.4%), and there were 37 (28.9%) patients with no comorbidities. The median time from admission to cardiac arrest was 12[6-18.5] days, the most common rhythm at the time of cardiac arrest was asystole in 94 (72.9%) patients, followed by pulseless electrical activity in 25 (19.4%); Ventricular dysrhythmias occurred in 7 (5.5%)of the cases. Finally, the median duration of CPR was 20[13.7-29] minutes. Conclusions: Survival of COVID-19 patients after in-hospital cardiac arrest was dismal, despite the adequate implementation of resuscitation protocols. Many of these patients were overweight or obese with comorbid conditions. The most common presenting rhythm was a non-shockable rhythm.
Abstract 13283: Utility of Ultrasound-Guided Measurements of Carotid Intima Media Thickness and Achilles Tendon Thickness in Patients With Familial Hypercholesterolemia
Authors: Tatiana Echeverry, Jamal Anthony, Robert D Fishberg
Journal: Circulation (2022)

Introduction: Ultrasound-guided measurement of carotid intima-media thickness (CIMT) can be used as a marker to predict future risk of atherosclerotic cardiovascular disease. Achilles tendons are the most common sites of xanthoma accumulation and can serve as a diagnostic index for patients with familial hypercholesterolemia (FH). We report a case of a patient with FH on PCSK9 inhibitor, who was followed up over the course of five-years to monitor the impact of the medication on CIMT and Achilles tendon thickness (ATT). Hypothesis: PCSK9 inhibitors are associated with reduction of carotid artery plaque and regression of tendon xanthomas. Methods: In a prospective study, at Overlook Medical Center in New Jersey, we followed up a 27-year-old patient with FH on PCSK9 inhibitor and high-dose statin diagnosed in 2006. After CABG, patient underwent CIMT and ATT in 2017, 2019 and at the five-year follow up in 2022. Results: In 2017, patient underwent ultrasound of the bilateral common carotids showed CIMT to be 0.91mm on right and 0.78mm on left and ultrasound of bilateral Achilles tendon showed ATT to be 0.91cm on right and 1.11cm on left. In 2019, ultrasound of bilateral common carotids showed CIMT to be 0.5mm on right and 0.57mm on left (mean CIMT reduction of 38%). Ultrasound of bilateral Achilles tendon showed ATT to be 1.04cm on the right and 0.98cm on the left (no significant change). In 2022, patient presented for the 5-year follow up, ultrasound of bilateral common carotids showed CIMT to be 0.55mm on right and 0.54 mm on left (no significant change) Ultrasound of bilateral Achilles tendon showed ATT to be 1.12cm on the right and 1.02cm on the left (no significant change). Conclusions: This case highlights the significant reduction in carotid artery plaque burden within the first two years of treatment with PCSK9 inhibitors. However, CIMT did not have a significant change after the five-year follow up. In addition, the patient didn’t have any significant changes in the Achilles tendon thickness throughout the five-years of treatment. This case illustrates how ultrasound-guided measurement of CIMT may help stratify ASCVD progression and quantify the effect of PCSK9 inhibitor on atherosclerotic plaque.
Abstract 11126: Longitudinal MRI-Based Superficial Femoral Artery Velocity Measurements in Peripheral Artery Disease: An Analysis of the Effect of Lipid Modification on Peripheral Artery Disease After Endovascular Intervention Trial (ELIMIT)
Authors: Ankita Sinharoy, Neeti Reddy, John K Lin, VIJAY NAMBI, Eric Y Yang, Panagiotis Kougias, Addison A Taylor, Alan Lumsden, Christie M Ballantyne, Gerd Brunner
Journal: Circulation (2022)

Introduction: Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. We analyzed longitudinal associations of non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the distal superficial femoral artery (SFA) with characteristics of PAD. Hypothesis: Longitudinal changes in MRI-based measures of SFA velocity are associated with changes in SFA lumen volumes in PAD. Methods: A total of 33 (11 diabetic, 22 non-diabetic) PAD patients, who completed baseline and 2-year follow-up MRI were included in this secondary analysis of ELIMIT. Electrocardiographically-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of the distal SFA territory. SFA lumen, wall, and total vessel volumes were averaged over all distal SFA MRI slices. Results: Baseline characteristics did not differ between diabetic and non-diabetic PAD patients (Table). Proximal and distal SFA velocity measures did not differ between baseline and 2-years (41.98: IQR (23.58, 72.6) cm/s; vs. 40.31: IQR (26.69, 61.29) cm/s; p=0.30, for maximum SFA velocity). The velocity amplitude (defined as the difference between the SFA minimum and maximum velocity) was significantly lower in the distal compared to the proximal SFA location at both baseline and at the 2-year visit (p=0.003, p&lt;0.001). In a pooled analysis of all 33 PAD patients, the 2-year change of the average SFA velocity was significantly associated with the 2-year change in the averaged SFA lumen volume (beta: 0.00011, r 2 : 0.175, p=0.017). In a subgroup analysis, a similar pattern was observed in diabetic patients (beta: 0.00006, r 2 : 0.714, p=0.001), but not in non-diabetics (beta: -0.000019, r 2 : 0.0095, p=0.68). Conclusion: Longitudinal 2D-PC-MRI SFA velocity changes are associated with 2-year SFA lumen changes. 2D-PC-MRI velocity measures may be of interest in assessing PAD.
Abstract 11321: The Characteristic, Procedural Safety and Middle Term Clinical Outcome Study of Chronic Total Occlusion Percutaneous Coronary Intervention Among Elderly Aged &lt;75 Years versus ≥75 Years
Authors: Heng Shee Kim, Shinji Imura, Motosu Ando, Yasuhiro Tarutani, Tsukiji Miwako, Yuuki Nakanishi, Yasuhiro Ono, Hosaka Fumitaka
Journal: Circulation (2022)

Introduction: The elderly is frequently related to frailty, comorbidities, and higher short- and long-term complications in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). The data was scarce. Thus, we aim to study the feasibility, safety, and outcome of CTO-PCI among the elderly aged &lt;75 years versus ≥75 years. Methods: We performed a consecutive retrospective analysis of 258 CTO-PCI attempted at Okamura Memorial Hospital, Japan, from September 2015 to April 2021 via the electronic health record. It was categorized into &lt;75 years and ≥75 years. All patients were analyzed for demographic, PCI, and follow-up details. We define target lesion failure (TLF) as the composite of cardiac-related death, target-vessel myocardial infarction (TVMI), and clinically driven target lesion revascularization (TLR). Regression analysis was done to identify specific risk factors for TLF. Results: Among attempted CTO-PCI, 177 (68.6%) &lt;75 years and 81 (31.4%) ≥75 years. There was no significant short-term or in-hospital complication between both groups, except a significantly higher wire or vessel perforation in the elderly (4.0% vs. 12.3%). Left main CTO-PCI was more frequent in the elderly (2.3% vs. 8.8%). The high success rate was no difference between both groups (97.7% vs. 97.5%), with a very high number of IVUS used in both groups (98.9% vs. 100%). The 1-year TLF was insignificant between both groups (10.2% vs. 8.6%). The contrast volume and non-hypertensive patients were found to significantly increase the risk of TLF in the elderly ≥75 Years (OR 1.02 - 17.93). Conclusion: Our study demonstrated that CTO-PCI in elderly patients is feasible, safe, and with excellent mid-term TLF outcomes compared with the younger patients. The identified risk factors related to TLF may be able to guide the management strategy in this group of patients. Thus, CTO in the elderly should not be deprived of an invasive PCI strategy when indicated.
Abstract 11951: Acute Cardiac Contractility Modulation Assessment in Conventional 2D Monolayers and 3D Engineered Cardiac Tissues Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: TK Feaster, Nicole Feric, Isabella Pallotta, Akshay Narkar, Maura Casicola, Michael Graziano, Rooz Sobbi, Ksenia Blinova
Journal: Circulation (2022)

Introduction: Cardiac contractility modulation (CCM) is a medical device therapy whereby non-excitatory electrical simulations are delivered to the myocardium during the absolute refractory period. We previously evaluated the effects of the standard CCM pulse parameters in isolated rabbit ventricular cardiomyocytes and 2D human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) monolayers, on flexible substrate. Hypothesis: In the present study, we sought to extend these results to 3D microphysiological systems to develop a human-based model to evaluate various clinical CCM pulse parameters in vitro. Methods: HiPSC-CMs were studied in conventional 2D monolayer format, on stiff substrate (i.e., glass), and as 3D human engineered cardiac tissues (ECTs). Cardiac contractile properties were evaluated by video-based analysis and custom force analysis. CCM pulses were assessed at varying clinical ‘doses’ using a commercial pulse generator. Robust response was observed at physiological Ca concentrations [1.8 mM] for 3D ECTs. Results: Under standard acute CCM stimulation 3D ECTs displayed enhanced contractile properties including increased peak contraction amplitude (i.e., force), and faster contraction and relaxation kinetics. Moreover, 3D ECTs displayed enhanced contractility in a CCM pulse parameter dependent manner. The observed effects subsided when the acute CCM stimulation was stopped and gradually returned to baseline. Under comparable conditions, conventional 2D monolayer hiPSC-CMs, on stiff substrate, displayed neutral response. Conclusions: These data represent the first study of acute CCM stimulation in a 3D hiPSC-CM model and provides a preclinical model to assess various CCM signals in human cardiac tissues prior to in vivo animal studies.
Abstract 11717: Expression of Tumor Endothelial Marker 1 in Cardiac Fibroblasts is Associated With Atrial Fibrosis and Regulates Cell Behaviors of Cardiac Fibroblasts
Authors: Yi-Heng Li, Ting-Chun Huang, Mu-Shiang Huang, Yu-Ning Hu, Hsing-Chun Chung
Journal: Circulation (2022)

Background: Tumor endothelial marker 1 (TEM1 or CD248) is a transmembrane protein that expresses in mesenchymal lineage-derived cells only during embryogenesis. Re-upregulation of TEM1 in fibroblasts has been found in hepatic fibrosis, renal fibrosis and wound healing. Atrial fibrosis plays an important role in atrial fibrillation (AF) and stroke. We evaluated TEM1 expression in atrial fibrosis and its physiological significance. Methods and Results: All data were presented as mean ± standard error. In 10 patients (pts) with AF undergoing indicated cardiac surgery and Maze procedure, left atrial (LA) appendage was excised. Immunofluorescence staining showed TEM1 expressed in LA cardiac fibroblasts (CFs) in AF pts but not in normal LA tissue purchased from the US Biomax, Inc. Sirius Red staining showed more LA fibrosis in AF than normal LA tissue (7.51±0.40% vs. 3.80±0.51%, p&lt;0.01). In AF pts, higher LA TEM1 expression detected by western blotting was associated with larger LA fibrosis. In 20 AF pts (15 men, mean age 57.5 ± 2.8 yrs) undergoing catheter ablation, LA blood samples were taken and soluble TEM1 (sTEM1) was measured by ELISA. Peak atrial longitudinal strain (PALS) measured by speckle tracking echocardiography before ablation was used as an atrial fibrosis marker. There was a significantly negative correlation of the sTEM1 levels in LA with PALS (ρ=-0.453, p&lt;0.05) indicating increased sTEM1 was associated with atrial fibrosis. In vitro study showed recombinant TEM1 protein (rTEM1) increased proliferation of cultured CFs (saline vs rTEM1 10, 50 and 100 nM, BrdU absorbance: 0.55±0.02 vs. 0.62±0.04 vs. 0.73±0.04 vs. 0.74±0.04, p&lt;0.05) and reduced starvation-induced apoptosis (cell death ELISA absorbance: 1.06±0.09 vs. 0.61±0.05 vs. 0.49±0.11 vs. 0.33±0.02, p&lt;0.05). Transwell assay showed rTEM1 induced increased CFs migration. Conclusions: The study results indicate that TEM1 upregulation in CFs is associated with atrial fibrosis and TEM1 changes the cell behaviors of CFs. Further studies are undergoing to clarify if TEM1 knockdown could alleviate atrial fibrosis.
Abstract 11707: How Age Affects the Association of Breast Arterial Calcification With Clinical Outcomes and Mortality
Authors: Alexandra V Sykes, Quan M Bui, Tara S Allen, Nora Belrose, Nitesh Nerlekar, Richard Mantey, Junhao Wang, Mohammad Eghtedari, Lori Daniels
Journal: Circulation (2022)

Background Cardiovascular disease (CVD) remains the number one cause of death in women. Current screening tools in this population do not identify all women who are at risk. Screening for breast artery calcification (BAC) via routine mammography is emerging as a risk enhancing tool; however, how risk prediction varies by age is unknown. Methods This single-center, retrospective study included 14,544 women who had a digital mammogram from 2008-2016. BAC was quantified with the Bradley score derived from an automated algorithm developed by CureMetrix; presence of BAC was defined as a Bradley score ≥10. Mortality data were collected after index mammogram by review of medical records. Adjusted hazard rations (aHR) were calculated using Cox regression models with interaction terms to evaluate the influence of age on the association between presence of BAC and mortality, after adjusting for age, diabetes, medications, race, current smoking, systolic blood pressure, total and HDL cholesterol, plus prior CVD. Results In the overall study population 8% had diabetes, 30% hypertension, 30% hyperlipidemia and 5% were current smokers. BAC was detectable in 522 of 9,027 (6%) of women age 40-59 years, 657 of 2,865 (23%) 60-69 years, and 702 of 1,358 (52%) 70+. Over mean follow-up of 4.2 years, there were 328 deaths (15.1%) among women with BAC. When subjects were separated by age, presence of BAC was associated with mortality among younger women (40-59 years: aHR 1.50 [95% CI 1.06-2.12]; 60-69 years: aHR 1.59 [95% CI 1.19-2.12], Figure ). Among women ages 70+, BAC was not a significant predictor of mortality (aHR 1.11 [95% CI 0.86-1.43]). There was a significant negative interaction effect of age with BAC for prediction of mortality (p &lt; 0.001). Conclusions: BAC is predictive of mortality, especially in younger women. BAC may be a useful screening adjunct to traditional CVD risk factors, to help identify women at an early age who may benefit from more targeted preventive measures. Figure
Abstract 11965: Cellular Senescence Produces Diastolic Dysfunction and Cardiac Hypertrophy With Aging in Mice
Authors: Mozhdeh Mehdizadeh, Martin Mackasey, Jean-Claude Tardif, Patrice Naud, Gerardo Ferbeyre, Martin Sirois, Eric Thorin, Jean-Francois Tanguay, Stanley Nattel
Journal: Circulation (2022)

Background: Age is a major risk factor for heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are poorly understood. Cellular senescence is an aging and stress related response; senescent cells (SCs) secrete bioactive substances that produce a variety of pathological changes. The role of senescence in HFpEF is unknown. Objectives: To study the effect of targeted deletion of SCs on cardiac function, structure and left ventricular (LV) pressure in an aging mouse model of HFpEF. Methods: We studied INK ATTAC mice, in which SCs undergo targeted clearance following treatment with a dimerizing agent, AP20187 (AP). Mice were treated with blinded AP or vehicle from 12 months to 18 months of age. Cardiac function and structure were studied with echocardiography. Contractility parameters were measured with a Millar catheter. The percentage of SCs in different cardiac-cell populations was analyzed with the use of Fluorescence-Activated Cell Sorting (FACS). Results: From 12 to 18 months, LV mass/LV diameter at end diastole (LVDd) and the LV anterior wall thickness at end diastole (LVAWd) increased in the vehicle group while they decreased in the AP group (LV mass/LVDd: %Δvehicle=+7.9± 3%, %ΔAP=-2±1.2%, P=0.005; LVAWd: %Δvehicle=+5.3±2.5%, %ΔAP=-3.5±1.6%, P=0.007) (Fig1A, B). E/e’ (echo) and isovolumic relaxation time indicated diastolic dysfunction in vehicle mice, and improved with AP (Fig1C, D). GFP bicistronic with p16 indicated SCs; FACS-purified fibroblasts (FBs) showed reduced GFP fluorescence (P=0.056) in the AP group, whereas immune and endothelial cells were not affected, suggesting that the anti-HFpEF effects of SC-clearance might be mediated through the clearance of senescent FBs (Fig1E). Conclusions: Our study points to a significant role of SCs, likely senescent FBs, in the pathophysiology of HFpEF. Modulating senescence might provide the basis for novel therapeutic approaches to HFpEF prevention and/or therapy.